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Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Viscarra JA, Rodriguez R, Vazquez-Medina JP, Lee A, Tift MS, Tavoni SK, Crocker DE, Ortiz RM - Physiol Rep (2013)

Bottom Line: However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin.To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses.Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1.

View Article: PubMed Central - PubMed

Affiliation: School of Natural Sciences, University of California, Merced.

ABSTRACT
Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation.

No MeSH data available.


Related in: MedlinePlus

Mean (±SE) plasma glucose (A) in response to early (n = 5) and late insulin infusions (n = 5), (B) in response to low- (LDG; n = 3) and high-dose (HDG; n = 4) glucagon-like peptide-1 (GLP-1) infusions plasma (GLP-1), and (C) the resulting glucose clearance rates (K) in response to the exogenous infusions. #denotes significantly (P < 0.05) different from early fasting; *denotes significantly (P < 0.05) different from baseline (T0); †denotes significantly (P < 0.05) different from late-fasting GTT; ‡denotes significantly (P < 0.05) different from LDG. Late GTT glucose, and early and late glucose clearance values adapted from (Viscarra et al. 2011a).
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fig02: Mean (±SE) plasma glucose (A) in response to early (n = 5) and late insulin infusions (n = 5), (B) in response to low- (LDG; n = 3) and high-dose (HDG; n = 4) glucagon-like peptide-1 (GLP-1) infusions plasma (GLP-1), and (C) the resulting glucose clearance rates (K) in response to the exogenous infusions. #denotes significantly (P < 0.05) different from early fasting; *denotes significantly (P < 0.05) different from baseline (T0); †denotes significantly (P < 0.05) different from late-fasting GTT; ‡denotes significantly (P < 0.05) different from LDG. Late GTT glucose, and early and late glucose clearance values adapted from (Viscarra et al. 2011a).

Mentions: Mean plasma glucose was reduced by 30 min and remained decreased throughout the sampling period during the insulin infusions in both the early- and late-fasted seals (Fig. 2A). A fasting effect on insulin-mediated glucose clearance was not detected (1.04 ± 0.18 vs. 1.02 ± 0.16 mg/dL per min) suggesting that peripheral tissue insulin sensitivity is not compromised with fasting duration.


Insulin and GLP-1 infusions demonstrate the onset of adipose-specific insulin resistance in a large fasting mammal: potential glucogenic role for GLP-1.

Viscarra JA, Rodriguez R, Vazquez-Medina JP, Lee A, Tift MS, Tavoni SK, Crocker DE, Ortiz RM - Physiol Rep (2013)

Mean (±SE) plasma glucose (A) in response to early (n = 5) and late insulin infusions (n = 5), (B) in response to low- (LDG; n = 3) and high-dose (HDG; n = 4) glucagon-like peptide-1 (GLP-1) infusions plasma (GLP-1), and (C) the resulting glucose clearance rates (K) in response to the exogenous infusions. #denotes significantly (P < 0.05) different from early fasting; *denotes significantly (P < 0.05) different from baseline (T0); †denotes significantly (P < 0.05) different from late-fasting GTT; ‡denotes significantly (P < 0.05) different from LDG. Late GTT glucose, and early and late glucose clearance values adapted from (Viscarra et al. 2011a).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3755502&req=5

fig02: Mean (±SE) plasma glucose (A) in response to early (n = 5) and late insulin infusions (n = 5), (B) in response to low- (LDG; n = 3) and high-dose (HDG; n = 4) glucagon-like peptide-1 (GLP-1) infusions plasma (GLP-1), and (C) the resulting glucose clearance rates (K) in response to the exogenous infusions. #denotes significantly (P < 0.05) different from early fasting; *denotes significantly (P < 0.05) different from baseline (T0); †denotes significantly (P < 0.05) different from late-fasting GTT; ‡denotes significantly (P < 0.05) different from LDG. Late GTT glucose, and early and late glucose clearance values adapted from (Viscarra et al. 2011a).
Mentions: Mean plasma glucose was reduced by 30 min and remained decreased throughout the sampling period during the insulin infusions in both the early- and late-fasted seals (Fig. 2A). A fasting effect on insulin-mediated glucose clearance was not detected (1.04 ± 0.18 vs. 1.02 ± 0.16 mg/dL per min) suggesting that peripheral tissue insulin sensitivity is not compromised with fasting duration.

Bottom Line: However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin.To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses.Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1.

View Article: PubMed Central - PubMed

Affiliation: School of Natural Sciences, University of California, Merced.

ABSTRACT
Prolonged food deprivation increases lipid oxidation and utilization, which may contribute to the onset of the insulin resistance associated with fasting. Because insulin resistance promotes the preservation of glucose and oxidation of fat, it has been suggested to be an adaptive response to food deprivation. However, fasting mammals exhibit hypoinsulinemia, suggesting that the insulin resistance-like conditions they experience may actually result from reduced pancreatic sensitivity to glucose/capacity to secrete insulin. To determine whether fasting results in insulin resistance or in pancreatic dysfunction, we infused early- and late-fasted seals (naturally adapted to prolonged fasting) with insulin (0.065 U/kg), and a separate group of late-fasted seals with low (10 pM/kg) or high (100 pM/kg) dosages of glucagon-like peptide-1 (GLP-1) immediately following a glucose bolus (0.5g/kg), and measured the systemic and cellular responses. Because GLP-1 facilitates glucose-stimulated insulin secretion, these infusions provide a method to assess pancreatic insulin-secreting capacity. Insulin infusions increased the phosphorylation of insulin receptor and Akt in adipose and muscle of early and late fasted seals; however the timing of the signaling response was blunted in adipose of late fasted seals. Despite the dose-dependent increases in insulin and increased glucose clearance (high dose), both GLP-1 dosages produced increases in plasma cortisol and glucagon, which may have contributed to the glucogenic role of GLP-1. Results suggest that fasting induces adipose-specific insulin resistance in elephant seal pups, while maintaining skeletal muscle insulin sensitivity, and therefore suggests that the onset of insulin resistance in fasting mammals is an evolved response to cope with prolonged food deprivation.

No MeSH data available.


Related in: MedlinePlus